COMPARISON OF ANTIHYPERTENSIVE EFFECT OF MOXONIDINE VERSUS CLONIDINE IN RENAL FAILURE PATIENTS.

COMPARISON OF ANTIHYPERTENSIVE EFFECT OF MOXONIDINE VERSUS CLONIDINE IN RENAL FAILURE PATIENTS. Journal of Drug Discovery And Therapeutics , (9).


INTRODUCTION High Blood Pressure
Blood pressure is the force of blood pushing against blood vessel walls as the heart pumps out blood, and high blood pressure, also called hypertension, is an increase in the amount of force that blood places on blood vessels as it moves through the body. Factors that can increase this force include higher blood volume due to extra fluid in the blood and blood vessels that are narrow, stiff, or clogged (1) .
In most cases, kidneys can eliminate most waste materials that our body produces. However, if the blood flow to the kidneys is affected, they are not working properly because of damage or disease, or if urine outflow is obstructed, problems can occur.

Functions of kidney include:
-Regulation of blood ionic composition (3) -Regulation of blood pH -Regulation of blood volume -Regulation of blood pressure -Maintenance of blood osmolarity -Production of hormones -Regulation of blood glucose level.

Kidney failure:
Kidney failure occurs when your kidneys lose the ability to filter waste from your blood sufficiently. Many factors can interfere with your kidney health and function (2) , such as: • toxic exposure to environmental pollutants or certain medications Chronic kidney disease (2) (CKD), also called chronic kidney failure, outline the gradual loss of kidney function. When CKD reaches an advanced stage, dangerous levels of fluid, electrolytes and wastes can build up in our body.
In the early stages of the disease, you may have few signs or symptoms. Treatment for chronic kidney disease focuses on slowing the progression of the kidney damage, usually by controlling the underlying cause. Chronic kidney disease can progress to end-stage kidney failure, which is fatal without artificial filtering (dialysis) or a kidney transplant.


Fetal developmental problem -if the kidneys do not develop properly in the unborn baby while it is developing in the womb.
 Malaria and yellow fever  Medications -NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin or ibuprofen.
 Illegal substance abuse -such as heroin or cocaine.
 Injury -a sharp blow or physical injury to the kidney(s)

Five types of kidney failure
There are five different types of kidney failure (4) :  Acute pre-renal kidney failure Insufficient blood flow to the kidneys can cause acute pre-renal kidney failure. The kidneys can't filter toxins from the blood without enough blood flow. This type of kidney failure can usually be cured once you and your doctor determine the cause of the decreased blood flow.
 Acute intrinsic kidney failure Acute intrinsic kidney failure can be caused by direct trauma to the kidneys, such as physical impact or an accident. Causes also include toxin overload and ischemia, which is a lack of oxygen to the kidneys.
The following may cause ischemia: severe bleeding. shock.
 Chronic pre-renal kidney failure When there isn't enough blood flowing to the kidneys for an extended period of time, the kidneys begin to shrink and lose the ability to function.

 Chronic intrinsic kidney failure
This happens when there is long-term damage to the kidneys due to intrinsic kidney disease. Intrinsic kidney disease is caused by a direct trauma to the kidneys, such as severe bleeding or a lack of oxygen.
 Chronic post-renal kidney failure A long-term blockage of the urinary tract prevents urination. This causes pressure and eventual kidney damage.

Pathophysiology of kidney disease
Figure1: Pathophysiology of kidney disease.

Symptoms:
Signs (4) and symptoms of kidney disease are often nonspecific, as kidneys are highly adaptable and able to compensate for lost function, signs and symptoms may not appear until irreversible damage has occurred. Some of the signs and symptoms of kidney disease may include:

Complications:
Chronic kidney disease can affect almost every part of your body. Potential complications may include:  Fluid retention, which could lead to swelling in your arms and legs, high blood pressure, or fluid in your lungs (pulmonary edema)  A sudden rise in potassium levels in your blood (hyperkalemia), which could impair your heart's ability to function and may be life-threatening

Prevention:
 To reduce your risk of developing kidney disease (4) :  Follow instructions on over-the-counter medications. Taking too many pain relievers could lead to kidney  damage and generally should be avoided if you have kidney disease. Ask your doctor whether these drugs are  safe for you.  Maintain a healthy weight.This involves increasing daily physical activity and reducing calories.
 Don't smoke. Cigarette smoking can damage your kidneys and make existing kidney damage worse. If you're a smoker, talk to your doctor about strategies for quitting smoking.
 Manage your medical conditions with your doctor's help. If you have diseases or conditions that increase your risk of kidney disease, work with your doctor to control them.

FIGURE 2: Biopsy of kidney
For kidney disease diagnosis, you may need certain tests and procedures, such as:  Blood tests. Kidney function tests look for the level of waste products, such as creatinine and urea, in your blood.
 Urine tests. Analyzing a sample of your urine may reveal abnormalities that point to chronic kidney failure and help identify the cause of chronic kidney disease.
 Imaging tests. Your doctor may use ultrasound to assess your kidneys' structure and size. Other imaging tests may be used in some cases.
 Removing a sample of kidney tissue for testing. Your doctor may recommend a kidney biopsy to remove a sample of kidney tissue. Kidney biopsy is often done with local anesthesia using a long, thin needle that's inserted through your skin and into your kidney. The biopsy sample is sent to a lab for testing to help determine what's causing your kidney problem.
 Chest X-ray -the aim here is to check for pulmonary edema (fluid retained in the lungs).
 Glomerular filtration rate (GFR) -GFR is a test that measures the glomerular filtration rate -it compares the levels of waste products in the patient's blood and urine. GFR measures how many milliliters of waste the kidneys can filter per minute. The kidneys of healthy individuals can typically filter over 90 ml per minute.

Treatment:
There is no current cure for chronic kidney disease (5) . However, some therapies can help control the signs and symptoms, reduce the risk of complications, and slow the progression of the disease.

 Kidney transplant
Depending on the underlying cause, some types of kidney disease can be treated. Often, though, chronic kidney disease has no cure.
Treatment usually consists of measures to help control signs and symptoms, reduce complications, and slow progression of the disease. If your kidneys become severely damaged, you may need treatment for end-stage kidney disease.
 Treating the cause Your doctor will work to slow or control the cause of your kidney disease. Treatment options vary, depending on the cause. But kidney damage can continue to worsen even when an underlying condition, such as high blood pressure, has been controlled.

 Treating complications
Kidney disease complications can be controlled to make you more comfortable. Treatments may include: o High blood pressure medications. People with kidney disease may experience worsening high blood pressure. Your doctor may recommend medications to lower your blood pressure -commonly angiotensinconverting enzyme (ACE) inhibitors or angiotensin II receptor blockers -and to preserve kidney function. High blood pressure medications can initially decrease kidney function and change electrolyte levels, so you may need frequent blood tests to monitor your condition. Your doctor will likely also recommend a water pill (diuretic) and a low-salt diet.
o Medications to lower cholesterol levels. Your doctor may recommend medications called statins to lower your cholesterol. People with chronic kidney disease often experience high levels of bad cholesterol, which can increase the risk of heart disease.
o Medications to treat anemia. In certain situations, your doctor may recommend supplements of the hormone erythropoietin, sometimes with added iron. Erythropoietin supplements aid in production of more red blood cells, which may relieve fatigue and weakness associated with anemia.
o Medications to relieve swelling. People with chronic kidney disease may retain fluids. This can lead to swelling in the legs, as well as high blood pressure. Medications called diuretics can help maintain the balance of fluids in your body.
o Medications to protect your bones. Your doctor may prescribe calcium and vitamin D supplements to prevent weak bones and lower your risk of fracture. You may also take medication known as a phosphate binder to lower the amount of phosphate in your blood, and protect your blood vessels from damage by calcium deposits (calcification).
o A lower protein diet to minimize waste products in your blood. As your body processes protein from foods, it creates waste products that your kidneys must filter from your blood. To reduce the amount of work your kidneys must do, your doctor may recommend eating less protein. Your doctor may also ask you to meet with a dietitian who can suggest ways to lower your protein intake while still eating a healthy diet.
o Your doctor may recommend follow-up testing at regular intervals to see whether your kidney disease remains stable or progresses.

Treatment for end-stage kidney disease:
If your kidneys can't keep up with waste and fluid clearance on their own and you develop complete or nearcomplete kidney failure and ∕or when the kidneys are functioning at less than 10-15 percent of normal capacity. Measures used so far -diet, medications, and treatments controlling underlying causes -are no longer enough.
The kidneys of patients with end-stage kidney disease cannot keep up with the waste and fluid elimination process on their own -the patient will need dialysis or a kidney transplant in order to survive and at that point, you need dialysis or a kidney transplant.
Most doctors will try to delay the need for dialysis or a kidney transplant for as long as possible because they carry the risk of potentially serious complications.

 Kidney dialysis
This is the removal of waste products and excessive fluids from blood when the kidneys cannot do the job properly any more. Dialysis has some serious risks, including infection.
There are two main types of kidney dialysis. Each type also has subtypes. The two main types are: o Hemodialysis: Blood is pumped out of the patient's body and goes through a dialyzer (an artificial kidney).
The patient undergoes hemodialysis about three times per week. Each session lasts for at least 3 hours.
Experts now recognize that more frequent sessions result in a better quality of life for the patient, but modern home-use dialysis machines are making this more regular use of hemodialysis possible.
o Peritoneal dialysis: The blood is filtered in the patient's own abdomen; in the peritoneal cavity which contains a vast network of tiny blood vessels. A catheter is implanted into the abdomen, into which a dialysis solution is infused and drained out for as long as is necessary to remove waste and excess fluid.

 Kidney transplant
A kidney transplant is a better option than dialysis for patients who have no other conditions apart from kidney failure. Even so, candidates for kidney transplant will have to undergo dialysis until they receive a new kidney.
The kidney donor and recipient should have the same blood type, cell-surface proteins and antibodies, in order to minimize the risk of rejection of the new kidney. Siblings or very close relatives are usually the best types of donors. If a living donor is not possible, the search will begin for a cadaver donor (dead person) (5) .

Potential future treatments:
Regenerative medicine holds the potential to fully heal damaged tissues and organs, offering solutions and hope for people who have conditions that today are beyond repair.
Regenerative medicine approaches include:  Boosting the body's natural ability to heal itself  Using healthy cells, tissues or organs from a living or deceased donor to replace damaged ones  Delivering specific types of cells or cell products to diseased tissues or organs to restore tissue and organ function

Lifestyle and home remedies:
As part of your treatment for chronic kidney disease, your doctor may recommend a special diet to help support your kidneys and limit the work they must do. Ask your doctor for a referral to a dietitian who can analyze your current diet and suggest ways to make your diet easier on your kidneys.
Depending on your situation, kidney function and overall health, your dietitian may recommend that you:  Avoid products with added salt. Lower the amount of sodium you eat each day by avoiding products with added salt, including many convenience foods, such as frozen dinners, canned soups and fast foods. Other foods with added salt include salty snack foods, canned vegetables, and processed meats and cheeses.
 Choose lower potassium foods. Your dietitian may recommend that you choose lower potassium foods at each meal. High-potassium foods include bananas, oranges, potatoes, spinach and tomatoes. Examples of lowpotassium foods include apples, cabbage, carrots, green beans, grapes and strawberries. Be aware that many salt substitutes contain potassium, so you generally should avoid them if you have kidney failure.
 Limit the amount of protein you eat. Your dietitian will estimate the appropriate number of grams of protein you need each day and make recommendations based on that amount. High-protein foods include lean meats, eggs, milk, cheese and beans. Low-protein foods include vegetables, fruits, breads and cereal  Patients with chronic kidney disease typically need to take a large number of medications.

 Treatments include:
o Anemia treatment Hemoglobin is the substance in red blood cells that carries vital oxygen around the body. If hemoglobin levels are low, the patient has anemia.
Some kidney disease patients with anemia will require blood transfusions. A patient with kidney disease will usually have to take iron supplements, either in the form of daily ferrous sulfate tablets, or occasionally in the form of injections.
o Phosphate balance People with kidney disease may not be able to eliminate phosphate from their body properly. Patients will be advised to reduce their nutritional phosphate intake -this usually means reducing consumption of dairy products, red meat, eggs, and fish.
o High blood pressure High blood pressure is a common problem for patients with chronic kidney disease. It is important to bring the blood pressure down to protect the kidneys, and subsequently slow down the progression of the disease.
o Skin itching Antihistamines, such as chlorpheniramine, may help alleviate symptoms of itching.
o Anti-sickness medications If toxins build up in the body because the kidneys don't work properly, patients may feel sick (nausea). Medications such as cyclizine or metaclopramide help relieve sickness.
o NSAIDs (non -steroidal anti-inflammatory drugs) NSAIDs, such as aspirin or ibuprofen should be avoided and only taken if a doctor recommends them (5) .

Complications:
If the chronic kidney disease progresses to kidney failure, the following complications are possible:

 Diet
A healthy diet, including plenty of fruits and vegetables, whole grains, and lean meats or fish will help keep blood pressure down.

 Physical activity
Regular physical exercise is ideal for maintaining healthy blood pressure levels; it also helps control chronic conditions such as diabetes and heart disease. Individuals should check with a doctor that an exercise program is suited to their age, weight, and health.

 Avoiding certain substances
Including abusing alcohol and drugs. Avoid long-term exposure to heavy metals, such as lead. Avoid long-term exposure to fuels, solvents, and other toxic chemicals.

Clonidine:
Description: Clonidine, an imidazoline-derivative hypotensive agent is a centrally-acting α 2 -adrenergic agonist. It crosses the blood-brain barrier and acts in the hypothalamus to induce a decrease in blood pressure. It may also be administered as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone.It may be used for differential diagnosis of pheochromocytoma in hypertensive patients.
Other uses for clonidine include: • prophylaxis of vascular migraine headaches • treatment of severe dysmenorrhea • management of vasomotor symptoms associated with menopause • rapid detoxification in the management of opiate withdrawal • treatment of alcohol withdrawal used in conjunction with benzodiazepines • management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension used in the treatment of attention-deficit hyperactivity disorder (6) .
clonidine also exhibits some peripheral activity. • May be used as an adjunct in the treatment of hypertension, • Also used as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone, • Used for differential diagnosis of pheochromocytoma in hypertensive patients.
• prophylaxis of vascular migraine headaches, • treatment of severe dysmenorrhea, • management of vasomotor symptoms associated with menopause, • rapid detoxification in the management of opiate withdrawal, • treatment of alcohol withdrawal used in conjunction with benzodiazepines, • management of nicotine dependence, • topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, • treatment of attention-deficit hyperactivity disorder (ADHD).

Pharmacodynamics:
Clonidine is an α-adrenergic agent that acts specifically on α 2 -receptors. α 2 -receptors regulate a number of signaling pathways mediated by multiple G i proteins, Gα i1 , Gα i2 , and G&alpha i3 . Stimulation of α 2 -receptors mediates effects such as inhibition of adenylyl cyclase, stimulation of phospholipase D, stimulation of mitogenactivated protein kinases, stimulation of K + currents and inhibition of Ca 2+ currents. Three G-protein coupled α 2 -receptor subtypes have been identified: α 2A , α 2B , and α 2C . Each subtype has a unique pattern of tissue distribution in the central nervous system and peripheral tissues. The α 2A -receptor is widely distributed throughout the central nervous system; it is found in the locus coeruleus, brain stem nuclei, cerebral cortex, septum, hypothalamus, and hippocampus. α 2A -receptors are also expressed in the kidneys, spleen, thymus, lung and salivary glands. The α 2C -receptor is primarily expressed in the central nervous system, including the striatum, olfactory tubercle, hippocampus and cerebral cortex. Low levels of the α 2C -subtype are also found in the kidneys. The α 2B -receptor is located primarily in the periphery (kidney, liver, lung and heart) with low levels of expression in the thalamic nuclei of the central nervous system. The α 2A -and α 2C -receptors are located presynaptically and inhibit the released of noradrenaline from sympathetic nerves. Stimulation of these receptors decreases sympathetic tone, resulting in decreases in blood pressure and heart rate. Sedation and analgesia is mediated by centrally located α 2A -receptors, while peripheral α 2B -receptors mediate constriction of vascular smooth muscle. α 2A -Receptors also mediate essential components of the analgesic effect of nitrous oxide in the spinal cord. Clonidine stimulates all three α 2 -receptor subtypes with similar potency. Its actions in the nervous system decreases blood pressure in patients with hypertension and decreases sympathetic overactivity in patients undergoing opioid withdrawal. Clonidine is also a potent sedative and analgesic and can prevent post-operative shivering in intensive and post-operative care. Its use in differential diagnosis of pheochromocytoma owes to the fact that hypertension in patients with pheochromocytoma is refractory to antihypertensive treatment with clonidine (6) . Absorption: Well absorbed following oral administration. Bioavailability following chronic administration is approximately 65%. Toxicity Oral LD 50 is 150 mg/kg in rat and 30 mg/kg in dog. Symptoms of overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.

Mechanism of Action
Clonidine works by stimulating alpha receptors that are located throughout the brain and spinal cord as well as other organs throughout the body such as the kidneys, liver, lungs, and heart.
Stimulation of the receptors in the hypothalamus causes signals to be sent that keep blood vessels relaxed, which allows the blood pressure to drop. Signals are sent to other parts of the brain to prevent the release of noradrenaline (hormone that increases the heart rate and constricts blood vessels),which may decreases the blood pressure and heart rate.
The alpha receptors throughout the body are stimulated by clonidine, causing the muscles that make up the walls of our internal organs and blood vessels to relax. This allows the blood pressure throughout the body to decrease.
Clonidine also used to relieve pain. This also involves stimulation of the alpha receptors, specifically the receptors on the spinal cord. When they are stimulated, the receptors send signals that block the feeling sensation throughout the spinal cord and these sensation-blocking signals will continue from the spinal cord out through the nerves that branch off from the spinal cord. Every area of the body served by the nerves will have the sensation of feeling blocked so that pain cannot be detected. This includes the brain, which is why clonidine can be used to relieve your migraines (7) .

Description
Moxonidine is a new-generation centrally acting antihypertensive drug approved for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors and calcium channel blockers are not appropriate or have failed to control blood pressure (6) . In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction.

Indication
For the treatment of mild to moderate essential or primary hypertension. Effective as most first-line antihypertensives when used as monotherapy

Pharmacodynamics
Antihypertensive agent whose site of action is the Central Nervous System (CNS), specifically involving interactions with I1-imidazoline and alpha-2-adrenergic rececptors within the rostral ventrolateral medulla (RSV).

Mechanism of action
Stimulation of central alpha 2-adrenergic receptors is associated with sympathoadrenal suppression and subsequent reduction of blood pressure. As this class was further explored it was discovered that sympathoadrenal activity can also be suppressed by a second pathway with a newly discovered drug target specific to imidazolines. Specifically, moxonidine binds the imidazoline receptor subtype 1 (I1) and to a lesser extent αlpha-2-adrenoreceptors in the RSV causing a reduction of sympathetic activity, reducing systemic vascular resistance and thus arterial blood pressure.
Moreover, since alpha-2-adrenergic receptors are considered the primary molecular target that facilitates the most common side effects of sedation and dry mouth that are elicited by most centrally acting antihypertensives, moxonidine differs from these other centrally acting antihypertensives by demonstrating only low affinity for central alpha-2-adrenoceptors compared to the aforementioned I1-imidazoline receptors (7) .
Absorption 90% of an oral dose is absorbed with negligible interference from food intake or first pass metabolism, resulting in a high bioavailability of 88%.

Protein binding
About 10% of moxonidine is bound to plasma proteins.

Metabolism
Biotransformation is unimportant with 10-20% of moxonidine undergoing oxidation reactions to the primary 4,5-dehydromoxonidine metabolite and a guanidine derivative by opening of the imidazoline ring (7) .
The antihypertensive effects of these 4,5-dehydromoxonidine and guanidine metabolites are only 1/10 and 1/100 the effect of moxonidine Oxidation on either the methyl group (pyrimidine ring) or on the imidazole ring of moxonidine results in the formation of the hydroxylmethylmoxonidine metabolite or the hydroxymoxonidine metabolite. The hydroxymoxonidine metabolite can be further oxidized to the dihydroxy metabolite or it can lose water to form the dehydrogenated moxonidine metabolite, which itself can be further oxidized to form an N-oxide. Aside from these Phase I metabolites, Phase II metabolism of moxonidine is also evident with the presence of a cysteine conjugate metabolite minus chlorine . Nevertheless, the identification of the hydroxymoxonidine metabolite with a high level of dehydrogenated moxonidine metabolite in human urine samples suggests that dehydrogenation from the hydroxy metabolite to the dehydrogenated moxonidine metabolite represents the primary metabolic pathway in human ] .
The cytochromes P450 responsible for the metabolism of moxonidine in humans have not yet been determined .
Ultimately, the parent moxonidine compound was observed to be the most abundant component in different biological matrices of urinary excretion samples, verifying that metabolism only plays a modest role in the clearance of moxonidine in humans.

Route of elimination
Elimination is nearly entirely via the kidneys with a majority (50 -75%) of overall moxonidine being eliminated unchanged through renal excretion. Ultimately, more than 90% of a dose is eliminated by way of the kidneys within the first 24 hours after administration, with only approximately 1% being eliminiated via faeces (7) . However, lower dosage adjustments and close monitoring is necessary in elderly and renal impairment patients due to reduced clearance. In particular, the exposure AUC can increase by about 50% following a single dose and at steady state in elderly patients and moderately impaired renal function with GFR between 30-60 mL/min can cause AUC increases by 85% and decreases in clearence to 52 %.

Toxicity
Contraindicated due to known hypersensitivity to an ingredient (Physiotens tablets contain lactose), heart failure, severe renal impairment, < 16 years old, >75 years old, bradycardia, severe bradyarrhythmia, sick sinus syndrome, second or third degree atrioventricular block, malignant arrhythmias.
Used with caution in patients with history of severe coronary artery disease (CAD), unstable angina, angioneurotic edema.
Pregnancy Category B3:Avoid use during pregnancy (inadequate data in pregnant woman) and lactation (maternal blood stream transfer to breast milk shown) unless benefit clearly justifies risk.
Lack of specific therapeutic experience in cases of intermittent claudication, Raynaud's disease, Parkinson's disease, epileptic disorders, gluacoma, and depression suggest moxonidine should not be used in such instances .
Carcinogenicity and genotoxicity does not appear significant.
Concurrent administration of other hypotensives or sedative and hypnotics can enhance the hypotensive effect and intensify sedation respectively.
Avoid concurrent Tricyclic Antidepressant (TCA) use to avoid reduction of monoxidine efficacy.
Generally well tolerated with dry mouth and headache the most common adverse effects Symptoms of overdose correlate with pharmacodynamicproperties:hypotension, sedation, orthostatic dysregulation, bradycardia, dry mouth with no specific counter-treatment known (7) .

REVIEW OF LITERATURE
Suresh V Sagarad (6) et al; (2013): conducted a study on "Prospective Real world experience of Moxonidine use in Indian Hypertensive patients-Prescription beyond current guidelines."In this study they focus on the use of Moxonidine. A prospective study conducted in which male and female patient with hypertension above 18 year's was selected and patient from op clinic with hypertension also were enrolled.There demographics with co-morbid illness of all patients were recorded. Patient's prescription and anti -hypertensive medications were also analysed and as a result a total of 990 patients were eligible during study period. Moxonidine were used in 4.5% patient's. One group with resistant hypertension and another group with intolerance to conventional first line drug. Moxonidine was given to resistant hypertension and renal failure patient's only. From this it was concluded that patients generally receive medication in accordance with recommendation and guidelines. Small but significant proportion of patient's may require use of Moxonidine to control high blood pressure.
Maria I Pikilidou (7) et al; (2013): conducted a study on "The Effect of anti-hypertensive drugs on Chronic kidney disease A Comprehensive review." From a randomized clinical trial and epidemiological evidence data identified hypertension as second most risk factors for CKD. CKD progress over years and early diagnosis and control of hypertension is important. In this study it was found out that a variety of anti-hypertensive drugs can be used in treatment of hypertension. In this the first choice of drug was renin angiotensin system inhibitors(enalapril,captopril).Other classes of drug including CCB (Amlodipine,verapamil),beta blockers (metoprolol,atenolol,nebivolo),Diuretics,aldosterone receptor blockers, alpha blockers and centrally acting antihypertensives (clonidine,moxonidine) etc,were used for treating hypertension . So they concluded that anti-hypertensive therapy should be obtained for optimal blood pressure control and variety of drugs are available.So every drug that effectively lowers hypertension is believed to be renoprotective.
Carinepoppe (8) et al; (2012): conducted a study on "Improving Quality of life in patients with CKD:influence of acceptance and personality." In this study they are evaluating whether acceptance of disease contributes to better physical and mental health related quality of life (PHQL and MHQL) and also impact of personality characteristics on acceptance of PHQL and MHQL.A cross sectional study conducted on 99 patients from OP clinic and had mean duration of CKD of 10.81 years and mean GFR by diet modification in renal disease. Regression analysis revealed that acceptance had a significant positive contribution of PHQL and MHQL. They conducted that acceptance is an important positive variable in accounting for HQL and provide a better understanding of psychological determinants of HQL in CKD. (9) et al;(2012), conducted astudy on "A comparison of thehaemodynamic and behaviouraleffects of moxonidine and clonidine in normotensive subjects."Randomised double-blind placebo controlled crossover study inhealthy normotensive patients.9 patients were selected and given single oral doses of moxonidine(200 mcg),clonidine (200 mcg) and placebo.Both active drugs significantly reduced blood pressure as comparedwith placebo.The hypotensive effect of clonidine was significantly greater. Moxonidine produced less adverse effects than clonidine, an equivalent hypotensive response was not demonstrated in normal subjects. (10) et al; (2012):conducted a study on"A Comparative Trial of Clonidine, Propranolol and Placebo in the Treatment of Moderate Hypertension." A double-blind cross over trial between clonidine, propranolol anda placebo in patients with moderate hypertension has been performed.32 patients completed the study which consisted of three treatmentperiods in random order of 3 months each.Both clonidine and propranolol was equipotent in reducing blood pressure.But clonidine has more side effect. (11) et al; (2011): conducted a study on "Quality of life in patients with chronic kidney disease.| Here 155 patents with stage 1-5 kidney disease and 36 hemodialysis were studied. Quality of life rated using SF-36 and functional status by karnofsky performance scale. It was found that QOL decreases in all stages of kidney disease. A reduction in physical function was observed in different stages of kidney disease. Individuals with high educational level displayed high physical component where as men and those with high income presented with better mental status. Older patients performance was worse on physical status where better on mental status .From this concluded that QOL s decreased in Renal patients in early stages of disease. (12) et al; (2005): conducted a study on "Health-related quality of life and estimates of utility in chronic kidney disease." In this study 205 persons with CKD and CKD stages 4 and 5 were tested two to eight times over two years with help of Kidney Disease Quality of Life Short Form 36 (KDQOL-36TM), Health Utilities Index (HUI)-3, and Time Trade-off (TTO) questionnaires .The relations among estimated glomerular filtration rate(e-GFR),and changes in health related quality of life and utility overtime were estimated using mixed effect regression models. From this mean scores on the KDQOL-36TM , HUI-3, and TTO suggested considerable loss of function and well-being in CKD relative to population norms. On cross-sectional analysis, lower levels of kidney function were associated with significantly lower scores on the SF-12 Physical Health Composite , the Burden of Kidney Disease subscale and the Effects of Kidney Disease subscale of the KDQOL-36TM. Kidney function was significantly associated with the TTO and global HUI-3 utility although these associations were attenuated after adjustment for diabetes. From this concluded that Health-related quality of life and estimates of utility are distressingly low in persons with CKD. Self-reported outcomes should be considered when evaluating health policy decisions that affect this population. (13) et al; (2004): conducted a study on "Moxonidine Normalizes Sympathetic Hyperactivity in Patients with Eposartan-Treated Chronic Renal Failure." In this study 42 patients were taken in which 22 patients are controlled and 11 stable patients with CRF, MSNA, BP and baroreceptor sensitivity were measured in the absence of antihypertensive drugs (except diuretics) during chronic eposartan therapy (600 mg for 6wk)and in 9 patients after moxonidine (0.2mgfor6wk) was added. BP, heart rate and MSNA were higher in patients than in 22 controls. After six weeks BP, Heart rate, MSNA were reduced with eposartantreatment.But addition of moxonidine to eposartan treatment further reduced BP, Heart rate, MSNA. The addition of moxonidine to angiotensin II antagonist treatment might be appropriate in reducing sympathetic hyperactivity. (14) et al;(2003):conducted a study on "Dose Relation of Blood Pressure Reduction with Moxonidine: Findings from Three Placebo-and Active-Controlled Randomized Studies." In this study three placebo-controlled trials in which 461 patients were selected and divided into 3 groups and blood pressure lowering effect of moxonidine with that of enalapril was compared.In all 3 groups enalapril reduce BP more than placebo and showed equivalence with moxonidine. Single dose of moxonidine 0.2-0.6mg reduced dose dependent, clinically relevant, statistically significant decrease in SiBP.

B. N. C. Prichard1
Farsang C (15) et al; (2001): conducted a study on "Moxonidine clinical profile" .Moxondine is a selective I1 receptor agonist used for hypertension .It act by inhibiting increased sympathetic tone and increases natriuresis and decrease blood pressure .So a daily dose of 0.2-0.6mg helps to reduce blood pressure in patients with mild to moderate hypertension. Various studies have been done and in a placebo controlled 6 week study 0.2-0.4mg moxonidine decreases both SBP and DBP and another double blinded randomised study for 8 weeks was conducted in 47 hypertensive patients and effect of moxonidine compared with enalapril 5-10mg and placebo. As compared to placebo, moxonidine and enalapril significantly decreases blood pressure. In a 6 months study 20 hypertensive patient with LVH was selected and also septum thickness was evaluated. 20 patients were given 0.6mg and 8 patients were given 0.4mg and 4 patients were given 0.2mg.After 9 months BP ,LVH and septum thickness decrease gradually. From this study it was concluded that moxonidine have several beneficial effect and is very useful in treatment of hypertension. (16) et al; (2000), conducted a study on"The Treatment of Hypertensive patients with a calcium antagonist or moxonidine: A Comparison." In this study Antihypertensive potency & tolerability of nifedipine&moxonidine in 229 patients where studied with primary hypertension.Screening phase of 7 days followed by a 21 day single blind placebo run & 26week active treatment phase.Initially patients received 0.2 mg moxonidine or 20mg nifedipine once a day. After 4 week dose was doubled. Both drugs are equieffective in treatment of hypertension 0.2mg moxonidine once a day is equal to 20mg/day nifedipine. Doubling of dose increased the responder rate to approximately 80%.The adverse event profile of moxonidine was better than nifedipine in the study. (17) et al; (2000): conducted a study on "I1 imidazoline agonist Moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives."Moxonidine is a I1 imidazoline receptor agonist that reduces blood pressure in hypertensives and inhibits central sympathetic activity. In this study 0.4mg moxonidne orally given to 8 volunteres to evaluate muscle sympathetic nerve activity and heart rate, bp. 24 hour blood pressure profile and hormone plasma level in 25 untreated hypertensives. In a double blinded placebo-controlled study.It resulted that moxonidie decreases muscle sympathetic nerve activity in both healthy volunteres and hypertensives. Plasma NE also decreasesd but epinephrine and renin level did not change .Also there is decrease in SBP and DBP who has given moxonidine and heart rate decrease in healthy subjects in hypertensives. plasmalevel,LDL,HDL and total cholestrol were not influenced by drug. It was concluded that moxonidine decreases SBP and DBP by inhibiting central nervous sympathetic activity. So new drug suitable for treatment of hypertension and cardiovascular diseases with increased sympathetic nerve activity.

AIM
To determine the antihypertensive effect of moxonidine versus clonidine in renal failure patients.

STUDY DESIGN
A prospective observational follow up study. SAMPLE SIZE 120 patients. 2 where, SD -standard deviation

EXCLUSION CRITERIA
• Those who are unable to give informed consent.

BRIEF PROCEDURE
A prospective observational study was conducted in Department of Nephrology at Pushpagiri Medical College Hospital on the topic "Comparison of Antihypertensive effect of Moxonidine Versus Clonidine in Renal Failure Patients".
The entire study was carried out only after getting approval from Institutional Ethics Committee. The selection of patients were based upon the inclusion and exclusion criteria.
All patients were provided with a brief introduction regarding the study and the confidentiality of the data. A written Informed Consent was obtained from the patient or care-giver.About 120 patients were selected. Patients data collection form was used for recording demographic details of the patients. It was a 6 month study in which blood pressure was recorded before and after treatment with drugs and after 3months of follow up.
Quality of life score was obtained using KDQOL-SF 36 questionnaires and Standard WHO questionnaires were used to monitor the adverse effect. Finally analyzed the results,      Systolic blood pressure indicates highly significant difference before and after treating with drugs.

FIGURE 9: EFFECT OF DRUGS ON DIASTOLIC BLOOD PRESSURE
Diastolic blood pressure indicates highly significant difference before and after treating with drugs.

FIGURE10: EFFECT OF DRUGS ON QUALITY OF LIFE
Quality of life indicates a highly significant difference before and after treating with drugs.

DISCUSSION
The patients who have satisfied the inclusion criteria where included in the study. A total of 120 patients were included in the study.
Age Group: In this study majority of patients comes under the 60-80 age group 67%), 36% comes under the age group of 40-60,9% comes under less than 40 age group and 8% comes under more than 80 years of age.
Gender: In this study 65% are male patients and 35% are female patients.
Marital status: In this study 96.7% patients are married and 3.3% patients are unmarried.
Social habits: In this study 49.2% patients have history of alcoholism and rest 50% are non -alcoholics. In this study 39.2% patients have history of smoking and rest 60.8% are non-smokers.
In this study blood pressure of the patients were monitored during the study period. Follow upwas conducted after3 months and their blood pressure was monitored. The patients had high blood pressure before the treatment and their blood pressure was reduced significantly during the treatment with the drugs as there p value shows a significant difference between the pairs (<0.05) The quality of life of the patient was measured using KDQOL SF 36 questionnaire. They showed a poor quality of life before the treatment but quality of life score improved significantly during the treatment phase.
The ADR of drugs were measured using WHO standard questionnaire.Both drugs showed a possible reaction and a more number of patients exhibited ADR when treated with Clonidine (45 out of 60) as compared to that of Moxonidine( 27 out of 60).

SUMMARY
A Prospective observational study on Comparison of Antihypertensive drug on CKD patients and effect of drug treatment on quality of life was assessed using KDQOL SF 36 which was carried out in Department of Nephrology, Pushpagiri Medical College Hospital Thiruvalla. Sample size consisted of 120 patients .The main objective of study was to determine which antihypertensive drug is more effective for CKD patients and also to determine the quality of life of patients after treating with drugs.
• In this study population majority of patients have age group of 60-80 years.
• In this study out of 120 patients 59(49.2%) are alcoholics and 47(39.2%) are smokers • In this study population the systolic blood pressure of patients before and after treatment and during follow up have a significant difference as the p-value is less than 0.05.
• In this study population the diastolic blood pressure of patients before and after treatment and during follow up have a significant difference as the p-value is less than 0.05.
• In this study population total SF 36 score before and after treatment with drugs moxonidine and clonidine have significant difference between the pairs.
• In this study more number of patients exhibited ADR when treated with Clonidine (45 out of 60) as compared to that of Moxonidine(27 out of 60).

CONCLUSION
To date, CKD remains an incurable disease and hypertension is the leading cause and / or seconds most risk factor for CKD. In this study primary objective was to focus the blood pressure reduction in patients with renal failure by comparing the antihypertensive action of Moxonidine and clonidine respectively. The secondary objective was to assess quality of life in CKD patients before and after the therapy. The quality of life was determined using KDQOL SF 36 questionnaire.
Our study confirms that the drug Moxonidine showed better result in reduction of blood pressure and improved the quality of life in patients who were on therapy with Moxonidine when compared to Clonidine. The drug Moxonidine also showed less adverse drug reaction when compared to that of Clonidine. Hence this study concluded that the newer antihypertensive drug Moxonidine is the best drug in CKD patients for the control of blood pressure and to improve the quality of life.